Preparation, characterization and pharmacokinetic studies of sulfobutyl ether-β-cyclodextrin-toltrazuril inclusion complex

被引：0

作者：

Xu D. ^{[1
]}

Li X. ^{[1
]}

Huang Y. ^{[1
]}

Tang Z. ^{[1
]}

Ran C. ^{[1
]}

Jing B. ^{[1
]}

Yin L. ^{[1
]}

Lin J. ^{[1
]}

Fu H. ^{[1
]}

Tang H. ^{[1
]}

Zhao X. ^{[2
]}

Shu G. ^{[1
]}

机构：

[1] Department of Basic Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan

[2] Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan

来源：

Journal of Molecular Structure | 2021年 / 1223卷

基金：

中国国家自然科学基金;

关键词：

Bioavailability; Inclusion complex; Pharmacokinetics; Sulfobutyl-ether-β-cyclodextrin; Toltrazuril;

D O I：

10.1016/j.molstruc.2020.128969

中图分类号：

学科分类号：

摘要：

In present study, a novel formulation was developed to enhance solubility, stability, and bioavailability of toltrazuril (Tol). Tol is a highly effective, broad-spectrum, low-toxic triazinone anticoccidial drug, but has poor water solubility. The inclusion complex of Tol with sulfobutyl ether-β-cyclodextrin (SBE-β-CD-Tol) was prepared by freeze-drying method and characterized via Infrared Fourier transformation (FTIR), Differential scanning calorimetry (DSC), Powder X-ray diffractometry (XRD), Scanning electron microscopy (SEM), and 1H NMR measurements. The comparative pharmacokinetic studies of Tol or SBE-β-CD were conducted by a single orally administered dose of 10 mg/kg in chickens to provide parameters for clinical applications. As a result, 1H NMR analysis showed that Tol may be embedded in the cavity of SBE-β-CD to form a stable inclusion complex. In addition, the stoichiometry obtained by the phase solubility study was 1:1. Moreover, the pharmacokinetics results showed that the SBE-β-CD-Tol exhibited higher absorption rate, prolonged the time of in vivo retention, and possessed better bioavailability relative to those of Tol. The present study revealed that the new SBE-β-CD-Tol can provide a practical and economical option for improving the solubility, stability and bioavailability of Tol. © 2020

引用

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